抗心律失常药RP62719对哺乳动物
心室肌K+电流的抑制
李玉荣 杨宝峰 徐长庆 周晋 杨永滨 张季叶 孙明智
摘 要: 使用全细胞膜片箝技术, 研究RP62719对内向整流钾电流(IK1)、瞬时外向钾电流(Ito)和延迟外向整流钾电流(IK)的作用,
并探讨其抗心律失常作用的机制。实验结果表明, 在指令电压为-100 mV时, RP62719可显著抑制豚鼠心室肌细胞IK1, 半数抑制浓度(IC50)为5.0±1.0
μmol/L。RP62719 10 μmol/L在+40 mV时对犬心室肌细胞Ito抑制率为84.0±4.4%, IC50为1.2±0.51
μmol/L。在+40 mV时, 50 μmol/L RP62719还可使豚鼠心室肌细胞IKstep 减少50.0±8.3%, IKtail减少56.0±4.9%,
IC50分别为4.2±0.8 μmol/L和3.3±0.75 μmol/L。提示RP62719抗心律失常的离子机制与其对IK1、Ito及IK的抑制有关。
关键词: RP62719; 内向整流钾电流; 瞬时外向钾电流; 延迟外向钾电流; 半数抑制浓度
(IC50)
学科分类号: Q463; R966
Inhibition of
transmembrane K+
currents in mammalian ventricular myocytes by
antiarrhythmic agent RP62719
LI Yu-Rong YANG Yong-Bin ZHANG Ji-Ye SUN Ming-Zhi
(Department of Physiology）
YANG Bao-Feng ZHOU Jin
（Department of Pharmacology)
XU Chang-Qing
（Department of Pathophysiology, Harbin
Medical University, Harbin 150086）
Abstract: The effect of RP62719 on the inward rectifier K+
current (IK1),transient outward K+ current (Ito)
and delayed outward K+ current (Ik) in isolated cardiac myocytes was
determined using the whole cell patch clamp technique in guinea pig and dog.
RP62719 decreased IK1 with an inhibitory concentration 50 (IC50
) of 5.0±1.0 μmol/L at -100 mV in guinea pig
ventricular cells. In dog ventricular myocytes, RP62719 inhibited Ito
by 84±4.4% with an IC50 of 1.2±0.51 μmol/L at +40
mV. In guinea pig ventricular cells, RP62719 decreased IK: IKstep
by 50.0±8.3% and IKtail by 56.0±4.9% at +40 mV, respectively. RP62719
inhibited IKstep with an IC50 of 4.2±0.8 μmol/L and IKtail with an IC50 of
3.3±0.75 μmol/L.Thus it is suggested
that the ionic mechanism of antiarrhymic effect by RP62719 may be due to its
inhibition of IK1,Ito and IK.
Key words: RP62719; IK1; Ito;
IK; inhibitory concentration 50 (IC50)
李玉荣（哈尔滨医科大学生理教研室）
杨宝峰（哈尔滨医科大学药理教研室）
徐长庆（哈尔滨医科大学病理生理教研室, 哈尔滨 150086）
周晋（哈尔滨医科大学药理教研室）
杨永滨（哈尔滨医科大学生理教研）
张季叶（哈尔滨医科大学生理教研）
孙明智（哈尔滨医科大学生理教研）
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Received 1999-12-23 Accepted 2000-07-04